Apolipoprotein A1 Gene Polymorphisms and Risk of Early Coronary Disease

Abstract

Genetic studies have identified polymorphisms at the apolipoprotein (Apo) A1 gene associated with HDL cholesterol and apolipoprotein levels, and a relationship between the severity of coronary artery disease and polymorphisms at the 5′-end of Apo A1 has been also reported. This study was designed to examine the relationship between polymorphism at the Apo A1 gene and the risk of early coronary artery disease. Furthermore, the association of the polymorphism with the classical risk factors was analyzed. A total of 176 male patients (mean age 43 ± 5 years) diagnosed as having unstable angina (53 cases) or myocardial infarction (123 cases) were prospectively evaluated. Data referring to hypertension, diabetes and tobacco consumption were recorded. The levels of total cholesterol, HDL cholesterol, Apo A1 and B and triglycerides were determined. DNA was obtained from the 176 patients and from 200 controls. In order to determine the Apo A1 genotypes at two polymorphic sites (G/A at –75 bp, and C/T at +83 bp), DNA was PCR amplified and digested with MspI. The frequency of carriers of the rare allele at the –75 bp site (M1–) was 0.34 in cases and 0.24 in controls (p < 0.05). The frequencies of the M1– allele among patients with angina and myocardial infarction were 0.43 (p = 0.009, angina vs. controls) and 0.30, respectively. No significant association between this polymorphism and other cardiovascular risk factors was found. No difference in the frequencies for carriers of the rare allele at the +83-bp polymorphism (M2) was observed among patients with angina (0.08 vs. 0.07) or myocardial infarction (0.04 vs. 0.07), and no association between this polymorphism and tobacco, hypertension and diabetes was noted. Patients carrying the rare M2– allele had a lower concentration of total cholesterol compared to those without this allele (183 ± 29 vs. 223 ± 54, p < 0.04) and HDL cholesterol was also lower among patients carrying the M2– (26 ± 4 vs. 33 ± 9, p < 0.02). In our community male patients with a diagnosis of coronary artery disease and age less than 50 years showed a higher frequency of the M1– allele at the –75-bp site of the Apo A1 gene. There was a significant increase in the frequency of the M1– allele in patients with unstable angina and no association with risk factors. In the +83-bp polymorphism there was no difference in the allelelic frequencies or the risk factors, except for the HDL cholesterol and total cholesterol where the patients with the allele M2– had lower levels than those homozygous for the M2+.

Apolipoprotein A1 gene polymorphisms as risk factors for hypertension and obesity

“…This frequency was similar to those observed in Nigerians (10.1%) [36], Japanese (13.5%) [37], other European populations (11.2-15.5%) [13,[38][39][40] and another Brazilian population composed of children (18.1%) [41]. Nevertheless, A allele frequency was lower than in Taiwanese (32%) [42], Spanish (20.3-24%) [17,43,44] and Omani (22%) [45] populations. Our findings also showed a decreased frequency of A allele when compared to an Italian centenarian population, reported as 18.3 and 25.4% for men and women, respectively [7].…”

Molecular genetics of atherosclerosis

“…Patients with premature atherosclerosis and mutations in genes encoding apoAI associated with deWciency of apoA-I and extremely low concentrations of HDL cholesterol have been described (Karathanasis et al 1987;Matsunaga et al 1991;Ordovas et al 1989). The apoA-1 G75GA polymorphism has been associated with coronary atherosclerosis (Chhabra et al 2005;Reguero et al 1998;Wang et al 1996).…”

An association analysis between ApoA1 polymorphisms and the high-density lipoprotein (HDL) cholesterol level and myocardial infarction (MI) in Japanese

“…Recent epidemiological studies have reported that common ApoA1 polymorphisms influence the levels of HDL-C and triglycerides (TG) (Ordovas et al 1986;Jeenah et al 1990;Pagani et al 1990;Talmud et al 1994;Groenendijk et al 2001b). In addition, several researchers reported associations between ApoA1 polymorphisms and CAD (Karathanasis et al 1983;Ordovas et al 1986;Reguero et al 1998), whereas others found no positive association (Ordovas et al 1991;Marshall et al 1994;Yamada et al 2002). One possible reason for the inconsistencies among previous association studies may be that almost all of these studies considered only a few restriction fragment-length polymorphisms instead of every polymorphism in the ApoA1gene.…”